Genetic influences in multiple myeloma
Lisa Mertens gives a brief outline of genetic influences in multiple myeloma.
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Multiple myeloma is a blood cancer that affects the bone marrow, the spongy-looking centre of the large bones. The word myeloma refers to marrow, while multiple myeloma explains that this cancer typically affects multiple bones in the body.
Small error with big effects
New blood cells are constantly needed to maintain a steady supply. The body forms an estimated 10 billion white blood cells per day. This takes place in the bone marrow, where blood stem cells use the genetic reference information (deoxyribonucleic acid (DNA)) to produce the different types of blood cells.
White blood cells defend the body from potential threats. Plasma cells are a white blood cell subtype and multiple myeloma begins from a single abnormal plasma cell.
A small error in the genetic reference information can produce an abnormal plasma cell. The abnormal cell is unable to build a useful antibody to help the immune system fight infection and instead produces a myeloma protein (M protein), also known as paraprotein. Para indicates something that is abnormal.
Potential damage from bone disease
Like a row of dominoes falling, the error repeats. The abnormal plasma cell multiplies, and more abnormal cells wander through the bone marrow and produce large amounts of paraprotein. The build-up of abnormal plasma cells and paraprotein cause the medical problems for the patient.
Often myeloma bone disease (MBD) develops, which weakens the bones so severely that they can break with little pressure. Myeloma bone disease mainly affects the bones in arms, legs, skull, spine, ribs and hips, as well as around the shoulders.
Multiple myeloma has different subtypes, depending on the changes in the abnormal plasma cell and the shape of the paraprotein.
Understanding the genetic influences and the myeloma subtype is valuable for prognosis and clinical treatment strategy.
Genetic influences: inherited and new
A combination of inherited and environmental factors is expected to contribute to myeloma.
Genetic errors can be passed on by one parent or both parents. Inherited changes in genes, such as BRCA1, BRCA2, BCMA or in genes responsible for DNA damage repair can increase the risk for myeloma.
If a family member develops this cancer, the risk for close biological family members increases slightly, even though myeloma is less likely to be inherited. Studies show that the inherited genetic risks differ between population groups. For example, African Americans in the USA are more likely affected by myeloma than other groups. This may be due to several factors but needs to be further investigated with a higher number of patients from different racial groups included in clinical studies.
Environmental influences can also cause genetic errors. This can be exposure to a high dose of radiation, a toxic substance (such as benzene, asbestos, some pesticides), or a virus.
Genetic information can be permanently changed, which increases the risk for errors in plasma cell production.
Certain job groups have a higher risk to develop myeloma if their work routine exposes them to chemicals, industrial dust, or fumes.
Apart from environmental factors, lifestyle aspects, such as low physical activity and excess body weight, also influence the risk to develop this cancer.
Higher risk with age
Increasing age is important in myeloma, because most cases are diagnosed in patients over 65 years. As the body ages, it experiences small genetic changes over time, which can collect and tip the scale towards a genetic error. This is a normal part of aging and highlights the importance of preventative cancer screening.
Common early symptoms that a doctor may want to investigate further include ongoing bone pain, bone fractures after minor injuries, and symptoms related to kidney function.
The scientific research into the causes and risk factors for multiple myeloma is ongoing, which means that constant efforts are made to understand how genetic errors in plasma cell formation drive the cancer. A major focus is to identify and establish new treatment strategies for myeloma patients.
MEET THE EXPERT
Dr Lisa Mertens obtained a PhD in Genetics at Stellenbosch University and works remotely for CeGaT, a CLIA laboratory headquartered in Germany. Her special interests are cancer vaccine research, fertility genetics, and hereditary genetic conditions. She is passionate about advocating for preventative cancer screening.
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